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Hemagglutination Inhibition (HAI) Antibody Landscapes after Vaccination with diverse H7 hemagglutinin (HA) proteins
bioRxiv - Immunology Pub Date : 2021-01-25 , DOI: 10.1101/2021.01.25.428062
Hyesun Jang , Ted M Ross

Background A systemic evaluation of the antigenic differences of the H7 influenza hemagglutinin (HA) proteins, especially for the viruses isolated after 2016, are limited. The purpose of this study was to investigate the antigenic differences of major H7 strains with an ultimate aim to discover H7 HA proteins that can elicit protective receptor-blocking antibodies against co-circulating H7 influenza strains. Method A panel of nine H7 influenza strains were selected from 3,633 H7 HA amino acid sequences identified over the past two decades (2000-2018). The sequences were expressed on the surface of virus like particles (VLPs) and used to vaccinate C57BL/6 mice. Serum samples were collected and tested for hemagglutination-inhibition (HAI) activity. The vaccinated mice were challenged with lethal dose of H7N9 virus, A/Anhui/1/2013. Results VLPs expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA. A putative glycosylation due to an A169T substitution in antigenic site B was identified as a unique antigenic profile of Italy/00. Introduction of the putative glycosylation site (H7 HA-A169T) significantly altered the antigenic profile of HA of the A/Anhui/1/2013 (H7N9) strain. Conclusion This study identified key amino acid mutations that result in severe vaccine mismatches for future H7 epidemics. Future universal influenza vaccine candidates will need to focus on viral variants with these key mutations.

中文翻译:

接种多种H7血凝素(HA)蛋白后的血凝抑制(HAI)抗体情况

背景对H7流感血凝素(HA)蛋白(尤其是2016年后分离出的病毒)的抗原差异的系统评价有限。这项研究的目的是调查主要H7株的抗原差异,最终目的是发现可以引发针对共同流行的H7流感株的保护性受体阻断抗体的H7 HA蛋白。方法从过去二十年(2000-2018年)鉴定的3,633株H7 HA氨基酸序列中选出9株H7流感毒株。序列在病毒样颗粒(VLP)的表面表达,并用于接种C57BL / 6小鼠。收集血清样品并测试血凝抑制(HAI)活性。用致死剂量的H7N9病毒攻击接种的小鼠,A / Anhui / 1/2013。结果表达H7 HA抗原的VLP引发了每个选择的H7 HA的广泛反应性抗体,除了A / Turkey / Italy / 589/2000(Italy / 00)H7 HA。归因于抗原位点B中A169T取代的推定糖基化被鉴定为Italy / 00的独特抗原谱。推定的糖基化位点(H7 HA-A169T)的引入显着改变了A / Anhui / 1/2013(H7N9)菌株的HA抗原结构。结论该研究确定了导致未来H7流行病的严重疫苗错配的关键氨基酸突变。未来的通用流感疫苗候选者将需要关注具有这些关键突变的病毒变体。归因于抗原位点B中A169T取代的推定糖基化被鉴定为Italy / 00的独特抗原谱。推定的糖基化位点(H7 HA-A169T)的引入显着改变了A / Anhui / 1/2013(H7N9)菌株的HA抗原结构。结论该研究确定了导致未来H7流行病的严重疫苗错配的关键氨基酸突变。未来的通用流感疫苗候选者将需要关注具有这些关键突变的病毒变体。归因于抗原位点B中A169T取代的推定糖基化被鉴定为Italy / 00的独特抗原谱。推定的糖基化位点(H7 HA-A169T)的引入显着改变了A / Anhui / 1/2013(H7N9)菌株的HA抗原结构。结论该研究确定了导致未来H7流行病的严重疫苗错配的关键氨基酸突变。未来的通用流感疫苗候选者将需要关注具有这些关键突变的病毒变体。结论该研究确定了导致未来H7流行病的严重疫苗错配的关键氨基酸突变。未来的通用流感疫苗候选者将需要关注具有这些关键突变的病毒变体。结论该研究确定了导致未来H7流行病的严重疫苗错配的关键氨基酸突变。未来的通用流感疫苗候选者将需要关注具有这些关键突变的病毒变体。
更新日期:2021-01-26
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